Isradipine is 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methylethyl ester having the chemical structure of formula (I).

Isradipine is therapeutically indicated for treating cardiovascular diseases. The cardiovascular diseases include angina, pectoris, hypertension and congestive heart failure. It is also used to treat high blood pressure.
Isradipine was disclosed in the German specification DE 2949491 and U.S. Pat. Nos. 4,466,972 and 4,567,271. DE 2949491 describes the general procedure to prepare 1,4-dihydropyridine derivatives. U.S. Pat. No. 4,466,972, GB02103203A, LU 0088342A9, EP 0000150A1, EP 0000150B1, AU 0538515B2 and other related patents describe the general method for the preparation of Benzoxadiazoles and their derivatives of general formula (II). These references in its entirety is hereby incorporated by reference into this application.

Where in R1 is —CH3 and R2 is —CH(CH3)2 it refers to Isradipine of formula (I). When R1 and R2 are not identical the general procedures described in these patent specifications produces a mixture of isomers of formula (II). These procedures for the preparation of Isradipine is characteristic of formation of the isomeric impurities, 1) 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid di-methyl ester of formula (III) and 2) 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid di-1-methylethyl ester of formula (IV) along pith Isradipine.
The U.S. Pat. No. 4,466,972 describes the preparation of compounds of general formula (II) by refluxing 2, 1, 3-benzoxadiazole-4-carboxaldehyde, keto ester and concentrated ammonia or a β-amino ester in presence of ethanol, followed by evaporation and purification by chromatography.

These symmetrical ester isomers (III) and (IV) are difficult to separate from the Isradipine and the separation is effected only by a chromatographic purifications. The drawback with the procedures described in these patents is that it is very difficult to produce the product in commercial quantities as it involves the purification of the product by chromatographic separations.
A single step process for the preparation of Isradipine was described in CH 661270. This procedure involves first reacting 2,1,3-benzoxadiazole-4-carboxaldehyde with isopropyl acetoacetate in the presence of catalytic quantities of acetic acid and piperidine in refluxing toluene, and further reacting it with methyl-β-aminocrotonate. The Isradipine formed in the reaction mixture was then. separated by toluene distillation followed by cyclohexane treatment. The crude product obtained was then crystallised from ethanol to get Isradipine. When we have repeated this process in our laboratory we got the Isradipine with substantially higher amount of symmetrical ester isomers (III) and (IV) are present in the product. Removal of these symmetrical ester isomers is very difficult even after several repurifications from ethanol.